scholarly journals Amyloid Fibrils of Mammalian Prion Protein Are Highly Toxic to Cultured Cells and Primary Neurons

2006 ◽  
Vol 281 (19) ◽  
pp. 13828-13836 ◽  
Author(s):  
Vera Novitskaya ◽  
Olga V. Bocharova ◽  
Igor Bronstein ◽  
Ilia V. Baskakov
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Cultured Cells ◽  
Primary Neurons

scholarly journals The uptake of tau amyloid fibrils is facilitated by the cellular prion protein and hampers prion propagation in cultured cells

2020 ◽  
Vol 155 (5) ◽  
pp. 577-591 ◽  
Author(s):  
Elena De Cecco ◽  
Luigi Celauro ◽  
Silvia Vanni ◽  
Micaela Grandolfo ◽  
Edoardo Bistaffa ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Cultured Cells ◽  
Cellular Prion Protein ◽  
Prion Propagation

scholarly journals The uptake of tau amyloid fibrils is facilitated by the cellular prion protein and hampers prion propagation in cultured cells

2020 ◽  
Author(s):  
Elena De Cecco ◽  
Luigi Celauro ◽  
Silvia Vanni ◽  
Micaela Grandolfo ◽  
Adriano Aguzzi ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Cultured Cells ◽  
Neuroblastoma Cells ◽  
Cellular Prion Protein ◽  
Brain Diseases ◽  
Gene Encoding ◽  
Prion Propagation ◽  
Prion Conversion ◽  
Tau Fibrils

AbstractTauopathies are prevalent, invariably fatal brain diseases for which no cure is available. Tauopathies progressively affect the brain through cell-to-cell transfer of tau protein amyloids, yet the spreading mechanisms are unknown. Here we show that the cellular prion protein (PrPC) facilitates the uptake of tau aggregates by cultured cells, possibly by acting as an endocytic receptor. In mouse neuroblastoma cells, we found that tau amyloids bind to PrPC; internalization of tau fibrils was reduced in isogenic cells devoid of the gene encoding PrPC. Antibodies against N-proximal epitopes of PrPC impaired the binding of tau amyloids and decreased their uptake. Surprisingly, exposure of chronically prion-infected cells to tau amyloids reduced the accumulation of aggregated prion protein; this effect lasted for more than 72 hours after amyloid removal. These results point to bidirectional interactions between the two proteins: whilst PrPC mediates the entrance of tau fibrils in cells, PrPSc buildup is greatly reduced in their presence, possibly because of an impairment in the prion conversion process.

scholarly journals Temperature-Dependent Structural Variability of Prion Protein Amyloid Fibrils

2021 ◽  
Vol 22 (10) ◽  
pp. 5075
Author(s):  
Mantas Ziaunys ◽  
Andrius Sakalauskas ◽  
Kamile Mikalauskaite ◽  
Ruta Snieckute ◽  
Vytautas Smirnovas
Keyword(s):  
Protein Aggregation ◽  
Prion Protein ◽  
Amyloid Fibrils ◽  
Prion Diseases ◽  
Morphological Properties ◽  
Large Sample Size ◽  
Structural Variations ◽  
Temperature Dependent ◽  
Protein Fibrils ◽  
Propagation Properties

Prion protein aggregation into amyloid fibrils is associated with the onset and progression of prion diseases—a group of neurodegenerative amyloidoses. The process of such aggregate formation is still not fully understood, especially regarding their polymorphism, an event where the same type of protein forms multiple, conformationally and morphologically distinct structures. Considering that such structural variations can greatly complicate the search for potential antiamyloid compounds, either by having specific propagation properties or stability, it is important to better understand this aggregation event. We have recently reported the ability of prion protein fibrils to obtain at least two distinct conformations under identical conditions, which raised the question if this occurrence is tied to only certain environmental conditions. In this work, we examined a large sample size of prion protein aggregation reactions under a range of temperatures and analyzed the resulting fibril dye-binding, secondary structure and morphological properties. We show that all temperature conditions lead to the formation of more than one fibril type and that this variability may depend on the state of the initial prion protein molecules.

scholarly journals 13C and 15N chemical shift assignments of mammalian Y145Stop prion protein amyloid fibrils

2016 ◽  
Vol 11 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Theint Theint ◽  
Philippe S. Nadaud ◽  
Krystyna Surewicz ◽  
Witold K. Surewicz ◽  
Christopher P. Jaroniec
Keyword(s):  
Chemical Shift ◽  
Prion Protein ◽  
Amyloid Fibrils ◽  
Chemical Shift Assignments

Tanshinones inhibit hIAPP aggregation, disaggregate preformed hIAPP fibrils, and protect cultured cells

2018 ◽  
Vol 6 (1) ◽  
pp. 56-67 ◽  
Author(s):  
Baiping Ren ◽  
Yonglan Liu ◽  
Yanxian Zhang ◽  
Mingzhen Zhang ◽  
Yan Sun ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Cultured Cells ◽  
Aβ Amyloid

Tanshinones act as common inhibitors to inhibit the aggregation of both hIAPP and Aβ, disaggregate preformed hIAPP and Aβ amyloid fibrils, and protect cells from hIAPP- and Aβ-induced toxicity.

scholarly journals The prion protein family member Shadoo induces spontaneous ionic currents in cultured cells

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Antal Nyeste ◽  
Claudia Stincardini ◽  
Petra Bencsura ◽  
Milica Cerovic ◽  
Emiliano Biasini ◽  
...  
Keyword(s):  
Family Member ◽  
Prion Protein ◽  
Cultured Cells ◽  
Ionic Currents ◽  
Protein Family

Prion protein protects against DNA damage induced by paraquat in cultured cells

2004 ◽  
Vol 37 (8) ◽  
pp. 1224-1230 ◽  
Author(s):  
Abderrahmane Senator ◽  
Walid Rachidi ◽  
Sylvain Lehmann ◽  
Alain Favier ◽  
Mustapha Benboubetra
Keyword(s):  
Dna Damage ◽  
Prion Protein ◽  
Cultured Cells

scholarly journals Alpha-synuclein from patient Lewy bodies exhibits distinct pathological activity that can be propagated in vitro

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Nicholas P. Marotta ◽  
Jahan Ara ◽  
Norihito Uemura ◽  
Marshall G. Lougee ◽  
Emily S. Meymand ◽  
...  
Keyword(s):  
Cellular Response ◽  
Amyloid Fibrils ◽  
Cultured Cells ◽  
Biological Activities ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Biological Behavior ◽  
Motor Deficits ◽  
Original Material

AbstractLewy bodies (LBs) are complex, intracellular inclusions that are common pathological features of many neurodegenerative diseases. They consist largely of aggregated forms of the protein alpha-Synuclein (α-Syn), which misfolds to give rise to beta-sheet rich amyloid fibrils. The aggregation of monomers into fibrils occurs readily in vitro and pre-formed fibrils (PFFs) generated from recombinant α-Syn monomers are the basis of many models of LB diseases. These α-Syn PFFs recapitulate many pathological phenotypes in both cultured cells and animal models including the formation of α-Syn rich, insoluble aggregates, neuron loss, and motor deficits. However, it is not clear how closely α-Syn PFFs recapitulate the biological behavior of LB aggregates isolated directly from patients. Direct interrogation of the cellular response to LB-derived α-Syn has thus far been limited. Here we demonstrate that α-Syn aggregates derived from LB disease patients induce pathology characterized by a prevalence of large somatic inclusions that is distinct from the primarily neuritic pathology induced by α-Syn PFFs in our cultured neuron model. Moreover, these LB-derived aggregates can be amplified in vitro using recombinant α-Syn to generate aggregates that maintain the unique, somatic pathological phenotype of the original material. Amplified LB aggregates also showed greater uptake in cultured neurons and greater pathological burden and more rapid pathological spread in injected mouse brains, compared to α-Syn PFFs. Our work indicates that LB-derived α-Syn from diseased brains represents a distinct conformation species with unique biological activities that has not been previously observed in fully recombinant α-Syn aggregates and demonstrate a new strategy for improving upon α-Syn PFF models of synucleinopathies using amplified LBs.

Sign in / Sign up

Export Citation Format

Share Document